基于参芪地黄汤治疗膜性肾病作用机制的网络药理学和分子对接技术分析

目的 基于网络药理学与分子对接技术探讨参芪地黄汤治疗膜性肾病（MN）的作用，并阐明其机制。 方法 通过中药系统药理学数据库和分析平台（TCMSP）筛选参芪地黄汤中7味中药所含有效成分及相应的靶蛋白，采用GeneCards数据库、孟德尔OMIM数据库和Drugbank数据库获取MN的相关基因靶点，采用Cytoscape软件构建“药物-化合物-靶点”网络，采用STRING 数据库和 Cytoscape 软件制作蛋白相互作用（PPI）网络，并进行拓扑学分析寻找核心靶点，采用分子对接软件对核心靶点与作用于核心靶点的活性成分进行分子对接，筛选出参芪地黄汤治疗MN的核心成分，采用 Bioconductor R 软件进行靶点基因本体论（GO）富集分析和京都基因和基因组百科全书（KEGG）通路富集分析。 结果 经筛选后获得参芪地黄汤的有效活性成分55个，药物作用靶点214个，MN相关靶点3 655个，获得药物疾病共同靶点144个，其中核心靶点5个，分别为蛋白激酶B1（AKT1）、表皮生长因子（EGF）、血管内皮生长因子A（VEGFA）、肿瘤蛋白P53（TP53）和表皮生长因子受体（EGFR）；基于分子对接技术筛选出3个潜在核心成分，包括槲皮素、木犀草素和薯蓣皂素；GO富集分析得出2 268个生物学过程、53 个细胞组成、175个分子功能；KEGG通路富集分析发现169条相关信号通路。 结论 参芪地黄汤可能通过降低炎症水平、抑制肾脏纤维化和维持肾小球滤过屏障的完整性等机制发挥对MN的治疗作用。

Analysis on network pharmacology and molecular docking technique based on mechanism of Shenqi Dihuang Decoction in treatment of membranous nephropathy

Objective To analyze the effect of Shenqi Dihuang Decoction in the treatment of membranous nephropathy （MN） based on network pharmacology method and molecular docking technique，and to clarify its mechanism. Methods The effective components and corresponding target proteins of 7 herbs of Shenqi Dihuang Decoction were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）；the target genes of MN were collected from the GeneCards database，OMIM database， and Drugbank database； the network of “components-compounds-targes” of Shenqi Dihuang Decoction was constructed by Cytoscape software； the protein-protein interaction network was constructed through STRING database and Cytoscape software， and the topological analysis was performed to identify the core targets； the molecular docking for the core targets with the active ingredients acting on them was performed to screen the core components of Shenqi Dihuang Decoction for the treatment of MN.Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Gene and Genomes （KEGG） pathway enrichment analysis were performed by Bioconductor R software. Results A total of 55 effective components，214 drug action targets，3 655 MN targets， and 144 intersection targets were obtained，including 5 core targets，which were protein kinase B1 （AKT1）， epidermal growth factor （EGF）， vascular endothelial growth factor A （VEGFA）， tumor protein P53 （TP53）， and epidermal growth factor receptor （EGFR）； three potential core components were screened based on the molecular docking technology， including quercetin， luteolin， and diosgenin；the GO enrichment analysis results revealed 2 268 biological processes， 53 cell compositions，and 175 molecular functions； the KEGG pathway enrichment analysis results revealed 169 related signal pathways. Conclusion Shenqi Dihuang Decoction may play a role in treatment of MN by reducing the level of inflammation， inhibiting the renal fibrosis and maintaining the integrity of glomerular filtration barrier.